**Abstract**

Extracellular vesicles (EVs) have in the recent decades gained an important stand as vehicles enabling cell-to-cell transport and communication. With the advanced development towards their clinical use and increasing versatility of potential applications, improving their tissue-specific targeting in order to enhance their functionality in drug delivery opened as a challenging engineering field. In the past, the question of specific intercellular contact has been addressed by decoration of the EV surface with agents able of specific target recognition. An attractive possibility here is the modification of strongly overexpressed EV surface marker proteins towards recognition of target cells. As these proteins are involved in a plethora of biological functions in EV biogenesis, cargo targeting and intercellular transfer, a minimal impact on protein architecture upon modifications is desirable, which would also increase the stability of the exosomal preparation intended for therapeutic use. This chapter focuses on the possibilities of engineering of the EV marker proteins towards antigen-recognition units broadly applicable to endow EVs with tissue-targeting functionality.

**Keywords:** extracellular vesicles, exosomes, tetraspanin, tissue-specific targeting, exosomal drug delivery
